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The Journal of Neuroscience, December 17, 2003, 23(37):11587-11601

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Development/Plasticity/Repair
Generation of Functional Radial Glial Cells by Embryonic and Adult Forebrain Neural Stem Cells

Christopher Gregg and Samuel Weiss

Genes & Development Research Group, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1

Radial glial cells (RGCs), a transient cell population present only in the developing CNS, function both as precursor cells and as scaffolds to support neuron migration. Their cellular origin, however, is not understood. In the present study, we tested the hypothesis that functional RGCs can be generated by multipotent neural stem cells. Embryonic forebrain neural stem cells were studied in vitro to identify putative signals that promote the generation and differentiation of functional RGCs, determined by their ability to support neuronal migration. Epidermal growth factor receptor signaling was sufficient to regulate both the generation and differentiation of morphologically, antigenically, and functionally defined RGCs. In contrast, fibroblast growth factor-2 promoted the generation of RGCs but was unable to support their differentiation. Although RGCs are not normally present in the adult brain, epidermal growth factor stimulated adult forebrain neural stem cells to generate RGCs in vitro and functional RGCs within the adult forebrain subependyma in vivo. Surprisingly, epidermal growth factor receptor signaling also promoted adult forebrain ependymal cells to dedifferentiate and adopt a radial morphology in vivo. These results suggest that neural stem cells can give rise to RGCs and that RGC-guided neuronal migration can be recapitulated in the adult CNS.

Key words: neural stem cell; radial glia; epidermal growth factor; fibroblast growth factor; neuron migration; regeneration

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Received July 8, 2003; revised October 23, 2003; accepted October 24, 2003.

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